Gut feeling gone wrong: Tangled relationship between disorders of gut-brain interaction and liver disease

Table 1 The table outlines converging pathophysiological mechanisms shared between disorders of gut-brain interaction, and liver diseases

Mechanism	DGBIs (e.g., IBS, FD)	Liver disease (e.g., MASLD, cirrhosis)	Shared pathophysiological outcomes
Microbiota dysbiosis[8,9]	Altered Firmicutes-to-Bacteroidetes ratio; increased proteobacteria; dysbiosis in > 70% of IBS patients	Decreased microbial diversity; increased Enterobacteriaceae and SIBO in 39%-50% cirrhotics	Immune activation; systemic inflammation endotoxemia; abnormal motility
Increased intestinal permeability[12,13]	Zonulin upregulation; CRH-induced tight junction breakdown; zonulin elevated in 55%-68% of diarrhea IBS patients	Decreased claudin-1, occludin, ZO-1 in cirrhosis and MASLD; tight junction protein loss in 60%-70% of cirrhosis; increased plasma LPS in 80%	Systemic inflammation; LPS-driven immune response; endotoxemia
Neuroimmune dysregulation[10,11]	HPA axis hyperactivity; increased CRH, visceral hypersensitivity; increased CRH and altered HPA axis in approximately 60% of IBS patients	Hepatic encephalopathy; ammonia and indole neurotoxicity	Cognitive impairment; visceral pain; mood disorders
Immune activation[14,15,18]	Increased IL-6, TNF-α, IL-1β; mucosal T-cell infiltration; IL-6 and TNF-α elevated in > 50% of IBS patients	TLR4 activation; Kupffer cell stimulation; systemic cytokinemia	Hepatocellular injury, fibrosis, chronic inflammation
Bile acid dysregulation[16,17]	Excess bile acids in colon; impaired FXR-FGF19 signaling; bile acid malabsorption in approximately 33% of IBS-diarrhea patients	Reduced bile acid recirculation; cholestasis; FXR/FGF19 pathway disruption in 60%-80% of MASLD; increased colonic bile acids	Dysbiosis, altered intestinal transit, diarrhea

IBS: Irritable bowel syndrome; FD: Functional dyspepsia; MASLD: Metabolic associated steatotic liver disease; SIBO: Small intestinal bacterial overgrowth; CRH: Corticotropin-releasing hormone; ZO-1: Zonula occludens-1; LPS: Lipopolysaccharides; HPA: Hypothalamus pituitary axis; IL: Interleukin; TNF: Tumor necrosis factor; TLR: Toll-like receptor; FXR: Farnesoid X receptor; FGF: Fibroblast growth factor.